Upregulation of β₃-Adrenergic Receptor mRNA in Human Colon Cancer: A Preliminary Study

Abstract

Objective: Tumor cell proliferation and migration, as well as metastasis formation, can be affected by several neurotransmitters, which therefore seem to be involved in the most important aspects of the malignant phenotype. In particular, modified β-adrenergic functions seem to be associated with proliferative alterations of numerous cancer cell lines. Pharmacological modulation of β-adrenoceptors (β-ARs) affects tumor cell growth in several experimental systems, and inhibition of metastasis formation by β-AR antagonists in in vivo models has recently been reported. Initial epidemiological studies have provided evidence that β-blockers can reduce cancer incidence, thus suggesting a possible role also in cancer prevention. Methods: Colorectal mucosa and cancer tissue were obtained from 41 patients. Specimens were taken within 1 h after the surgical procedure and stored at –80°C until assayed. The gene expression of β₁-, β₂- and β₃-ARs in cancer tissue and normal surrounding mucosa was measured by real-time PCRs. Results: Comparable levels of β₁- and β₂-AR mRNA were found to be expressed in normal mucosa and cancer tissues. A significant difference in β₃-AR mRNA levels between normal mucosa and cancer tissues was found, with β₃-AR mRNA expression being twice as high in cancer tissue than normal mucosa. Conclusion: The results of the present study indicate that β₃-AR mRNA is upregulated in human colon cancer, thus suggesting the possible involvement of β₃-AR in malignant transformation in the human colon.

β3-adrenoreceptor blockade reduces tumor growth and increases neuronal differentiation in neuroblastoma via SK2/S1P2 modulation

“…Until a few years ago, the β2-AR subtype was identified as the most involved in tumor-related pathways [13]. However, an aberrant expression of the β3-AR subtype has been recently shown in several cancers, such as leukemia, vascular tumors, colon carcinoma [14][15][16], and many other human cancers [17]. Moreover, recent studies have shown that the use of selective β3-AR antagonists in melanoma was effective in reducing tumor growth via direct antitumoral effects [18] and by affecting tumor microenvironment reactivity [19].…”

Norepinephrine promotes tumor microenvironment reactivity through β3-adrenoreceptors during melanoma progression

“…β3-AR plays a key role in the pathophysiology of the cardiovascular system and has been recently correlated with de novo angiogenesis in models of retinal vascular proliferation [8–10]. Moreover, β3-AR mRNA aberrant expression has been reported in human cancers, such as leukemia, vascular tumors and colon carcinoma [5, 11, 12]. Recently, β 3 -ARs has been found to be expressed by murine melanoma B16F10 cells and by endothelial cells of the tumor vasculature [13, 14].…”

β3-Adrenoceptor Agonists and (Antagonists as) Inverse Agonists

“…A twofold higher expression of b 3 -AR mRNA in cancer tissue than normal one was found, thus suggesting a b 3 -AR possible involvement in the human colon tumor processing (Perrone et al, 2008a). Pharmacological modulation of b-ARs affects tumor cell growth in several experimental systems, and inhibition of metastasis formation by b-ARs antagonists in in vivo models has been ascertained.…”